PSA Doubling Time Predicts Distant Metastasis

PSA Doubling Time Predicts Distant Metastasis

SAN ANTONIOIn a retrospective study of prostate cancer patients
with a rising PSA after external beam radiation therapy, pretreatment
factors appeared to have little independent influence on the
development of metastatic disease. However, two post-treatment
factors, PSA doubling time and time to onset of a rising PSA, were
found to be major determinants of metastatic relapse, Lewis G. Smith
III, MD, reported at the 41st Annual Scientific Meeting of the
American Society for Therapeutic Radiology and Oncology (ASTRO).

Patients in the cohort represented an average spectrum of patients
who received radiation therapy during the 1980s and 1990s for
prostate cancer, Dr. Smith said. He added that even those who
developed a rising PSA still had fairly good outcomes. Their
overall survival was the same as predicted survival, and I think that
is a key significant point, he said.

The parent population consisted of 1,119 patients, all treated
between 1987 and 1997. All patients had T1 to T3 disease, and their
pretreatment PSA levels ranged from 0.3 to 150 ng/mL (median, 8.4
ng/mL).

The external beam radiation dose varied from 60 to 78 Gy (median, 68
Gy). None of the patients had received androgen ablation at the time
of initial therapy. Follow-up ranged from 12 to 146 months (median,
59 months).

Of this parent population, there were 357 patients who developed a
rising PSA level (the test cohort). The time to onset of the rise in
PSA was from 1 to 100 months (median, 20 months). Follow-up after the
onset of the rise of PSA ranged from 3 to 132 months (median, 53
months).

Treatment for the rising PSA was at the discretion of the
investigating physician: 91 patients received no additional
treatment; 216 patients were given androgen ablation (181 for a
rising PSA and 35 who were diagnosed with distant metastasis at the
time of the onset of the rise in PSA); 42 patients underwent
cryosurgery; and 8 patients underwent prostatectomy.

Local control was a main issue for the test patients, Dr.
Smith said. At 5 years, 50% had failed locally, and at 8 years, 59%
had failed locally.

Freedom from distant metastasis was 87% at 5 years, and 69% at 8
years. And this is from the point of the rise in PSA, not from
the time of treatment, he said.

On first analysis of the information, it appeared that stage, Gleason
score, and pretreatment PSA were going to be of importance.
However, when we re-analyzed data with 8 years of follow-up and
added a few more patients and looked more thoroughly, we found that
we really couldnt find any pretreatment factors that, under
multivariate analysis, would indicate a predictor for distant
metastasis, Dr. Smith said.

On multivariate analysis for distant metastasis, only two factors
were found to be significant: PSA doubling time and onset of a rise
in PSA. PSA doubling time of greater than 12 months was favorable for
this group of patients, and the onset of a rise in PSA beyond 12
months was also favorable.

The researchers analyzed data for the patients untreated for rising
PSA as well as for the patients with distant metastases at the time
of rising PSA. Basically, the worst case and the best case
scenarios, Dr. Smith said. The untreated patients had a median
PSA doubling time of 23 months vs 6 months for the metastatic
patients. And the median onset of a rise in PSA following treatment
was 20 months for the untreated patients vs 10 months for those
patients who were diagnosed with metastatic disease.

For the patients who received early androgen ablation for a rising
PSA, two factors were predictive of distant metastasis: Gleason score
and time to rise in PSA. Additionally, the PSA doubling time
was bordering on significance, he said.

On multivariate analysis, only the time to onset of the rise in PSA
was significant in these patients. Those who had a rise in PSA 12
months or longer after treatment had roughly an 82% freedom from
distant metastasis at 8 years, while those patients whose PSA level
began to rise less than a year from the time of initial treatment had
only a 27% probability of being free from distant metastasis at 8
years.

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